Targeting High Risk Populations With Enhanced Reactive Focal Mass Drug Administration in Thailand (COMBAT)

April 23, 2026 updated by: University of California, San Francisco

Targeting High-risk Populations With Enhanced Reactive Focal Mass Drug Administration: A Study to Assess the Effectiveness and Feasibility for Plasmodium Falciparum and Plasmodium Vivax Malaria in Thailand

This study assesses the effectiveness of reactive focal mass drug administration (rfMDA), targeting both village and forest working populations, compared to control for reducing the health promotion hospital-level (sub-district) incidence and prevalence of P. falciparum and P. vivax within five provinces in Thailand.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Thailand currently has a well-developed and robust surveillance system based on detailed mapping of all cases to the village foci level and stratification of response. In fiscal year 2019, 5,833 cases of malaria were reported with 83.0% P. vivax and 12.9% P. falciparum; nine deaths were reported. This represents a 20.8% decrease in total cases from fiscal year 2018. Currently, there are 701 "A1" villages in 44 provinces.

The research proposed here will evaluate the effectiveness and feasibility of enhanced reactive focal mass drug administration, results of which will have direct implications for continued roll out the community-led foci management, providing practical guidance that other malaria programs can utilize. Responding to the malaria among high risk populations is a requirement from the National Malaria Elimination Strategy in Thailand. Additionally, Thailand has experienced outbreaks related to forest work over the past several years, and consequently the Department of Vector Borne Disease (DVBD) is interested in introducing more aggressive parasite elimination strategies, including rfMDA for P. falciparum and P. vivax specifically targeting high-risk populations to interrupt transmission and rapidly accelerate elimination.

Study Type

Interventional

Enrollment (Actual)

14977

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Thailand
      • Bangkok, Thailand
        • Division of Vector Born Diseases, Ministry of Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria for rfMDA:

  • Index cases: Presented as a confirmed malaria case to an intervention health facility or village malaria worker, and lives in a village within a selected intervention subdistrict, or worked or spent at least one night at a forest or forest-fringe site in the past 30 days located within an intervention subdistrict
  • Village residents: Lives in a village within a selected intervention subdistrict area and in one of the five households closest to the residence of an index case of malaria
  • Co-worker/traveler referral: Worked or traveled and spent at least one night in forest in past 30 days in same location within an intervention subdistrict as an index case of malaria
  • All participants: Willing and available to participate in the study and informed consent for participant under the age of 18 will be provided by the parent or guardian. Participants for focus group discussions (FGDs) and key informant interviews (KIIs); 18 years of age or older

Exclusion Criteria:

• For rfMDA:

  • Previous participation in the study as a result of any rfMDA event in the past 30 days
  • Individuals with severe disease or drug contra-indications will be excluded from the treatment component only
  • Artesunate-Mefloquine: Pregnancy in the first trimester, or known drug allergy
  • Use of Mefloquine within 60 days of first treatment prior to enrollment date.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: reactive focal mass drug administration (rfMDA)
Reactive FMDA (rfMDA) led by VMVs in response to cases in study area sub-district, in both villages and forest workers; quantitative G6PD testing for all individuals and 14-day PQ for G6PD non-deficient.
Other: Case Management and Follow-up

Individuals will be told of their test result and a positive test result on either RDT will prompt treatment as per the national treatment guidelines.

  • Individuals with P. falciparum infection will be treated with an age-appropriate course of dihydroartemisinin/piperaquine (DHAP) or artesunate-pyronaridine (Pyramax) and PQ.
  • At all study sites in Thailand, patients with a P. vivax infection identified by the standard combination RDT will be tested by the VMV and Health Promotion Hospital (HPH) staff member using the quantitative G6PD RDT. G6PD normal individuals will be treated with Chloroquine (CQ) and a 14-day course of primaquine (PQ). G6PD deficient individuals will receive CQ alone and referred to the nearest health facility for further primaquine management decisions.
Other: Reactive focal mass drug administration (rfMDA)

Reactive focal mass administration (rfMDA) will be implemented around the index case household and to forest co-workers/co-travelers in Thailand. The VMV will conduct the investigation visit within 7 days after the notification of the index case. All members of the index case's household as well as all members of the nearest five households around the index case's household, including temporary visitors will be invited to participate in the study and to be treated for malaria without a malaria test. After obtaining participants' or parents/guardians' consent, the VMV will proceed with the participant questionnaire, and all consenting household members will be tested for G6PD using the G6PD quantitative test prior to administration of antimalarials.

For rfMDA, all eligible participants will be offered artesunate-mefloquine (AS-MQ). Per national policy, a 14-day course of primaquine will be administered to G6PD non-deficient study participants.
Active Comparator: Control
Standard of care including case management through health facilities and malaria posts/VMVs; village-based RACD conducted by district staff in some areas.
Other: Case Management and Follow-up

Individuals will be told of their test result and a positive test result on either RDT will prompt treatment as per the national treatment guidelines.

  • Individuals with P. falciparum infection will be treated with an age-appropriate course of dihydroartemisinin/piperaquine (DHAP) or artesunate-pyronaridine (Pyramax) and PQ.
  • At all study sites in Thailand, patients with a P. vivax infection identified by the standard combination RDT will be tested by the VMV and Health Promotion Hospital (HPH) staff member using the quantitative G6PD RDT. G6PD normal individuals will be treated with Chloroquine (CQ) and a 14-day course of primaquine (PQ). G6PD deficient individuals will receive CQ alone and referred to the nearest health facility for further primaquine management decisions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Confirmed P. falciparum and P. vivax malaria parasite incidence
Time Frame: 3 months
Defined as the number of outpatient (OPD) malaria confirmed and suspected cases per person per year for each sub-district, as ascertained from the health facility registers, utilizing administrative catchment population size estimates for the exposure denominator.
3 months
PCR-based P. falciparum and P. vivax parasite prevalence in sampled sub-districts
Time Frame: 3 months
Defined as the proportion of individuals ≥18 months old with P. falciparum or P. vivax infection (detected by PCR) out of all individuals ≥18 months tested within the end line survey.
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Population coverage of rfMDA interventions
Time Frame: 3 months
This indicator will be measured in two ways. Operational program coverage will be defined as the proportion of individuals ≥18 months old and households visited and offered the rfMDA interventions within the target areas per time period. Effective program coverage is defined as the proportion of individuals (≥18 months old) that agreed to participate in the rfMDA intervention among all individuals ≥18 months old eligible to participate in the intervention in the target population per time period.
3 months
Feasibility of conducting rfMDA at the community level
Time Frame: 3 months
Feasibility will be determined based upon a combination of population coverage data, responses of provincial, district, and health staff, VMWs, and community members to interviews and focus groups at baseline and end line, village malaria workers (VMWs) competency checklists at baseline, midline, and end line, and cost data.
3 months
Acceptability of rfMDA approach
Time Frame: 3 months
Acceptability will be determined based upon refusal rates during interventions and responses of community members and VMWs to end line questionnaire, interviews, and focus groups.
3 months
Adverse event rate
Time Frame: 3 months
Safety measures will include the adverse event rate amongst treated individuals and hemoglobin measurement pre and post treatment for individuals receiving PQ.
3 months
Operational feasibility of glucose-6-phosphate dehydrogenase (G6PD) testing and referral
Time Frame: 3 months
Operational feasibility of G6PD testing and referral will be determined by responses of health staff and VMWs to interviews and focus groups at baseline and end line and competency checklists at baseline, midline, and end line, the proportion of P. vivax cases with a valid G6PD result, and proportion of referred cases presenting at a health facility for G6PD testing.
3 months
Assessment of P. vivax treatment adherence
Time Frame: 3 months
Treatment adherence will be determined by the proportion of P. vivax cases with physical evidence of adherence through pill count and the P. vivax relapse rate across study arms.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

Centers for Disease Control and Prevention
University of Massachusetts, Amherst
Tulane University School of Public Health and Tropical Medicine
Center for Malariology, Parasitology, and Entomology

Investigators

  • Principal Investigator: Adam Bennett, MA, PhD, University of California, San Francisco
  • Principal Investigator: Cheewanan Lertpiriyasuwat, MD, Ministry of Health, Thailand

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2020

Primary Completion (Actual)

March 31, 2022

Study Completion (Actual)

March 31, 2022

Study Registration Dates

First Submitted

September 13, 2021

First Submitted That Met QC Criteria

September 13, 2021

First Posted (Actual)

September 22, 2021

Study Record Updates

Last Update Posted (Actual)

April 29, 2026

Last Update Submitted That Met QC Criteria

April 23, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 19-04062020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be shared with any parties outside of the study team.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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